Obsessive-compulsive disorder has been studied from several different perspectives since the beginning of this project in 1980. A major focus in this past year has been the continued investigation of an abnormality in serotonergic function in this syndrome. Previously we showed that the tricyclic antidepressant clomipramine was specifically anti-obsessional, in contrast to several other antidepressants. As clomiprimine is considerably more potent than other tricyclic antidepressants in its serotonergic effects, we hypothesized that drugs with selective actions on serotonin receptors would affect obsessional symptoms. Indeed, administration of the selective serotonin postsynaptic receptor agonist m-chlorophenylpiperazine (m-CPP) appeared to increase obsessional symptoms and anxiety in patients with obsessive-compulsive disorder but not in healthy controls. By contrast, the post-synaptic serotonin receptor antagonist, metergoline was associated with a slight decrease in obsessional symptoms. The obsession-inducing effects of m-CPP appear to be blocked by chronic clomipramine administration. Continued studies of cerebral blood flow in obsessive-compulsive patients have revealed an increase in cortical flow during "imaginal flooding" and a profound decrease in cortical flow during actual exposure to the obsessional stimulus. Finally, we continue to track the natural course of this disorder with follow-up studies of patients treated between 1980-1983.